Renal disease

Examples of renal diseases are kidney stones, kidney infections (pyelonephritis), chronic kidney disease and renal failure, glomerulonephritis (including IgA nephropathy, Goodpasture syndrome, lupus nephritis), polycystic kidney disease and renal cancer. Diabetes and high blood pressure contribute to making chronic kidney disease the most prevalent renal disease in high income countries. All of these conditions impair the function of the kidneys, affect fluid balance and urine production, and impede efficient excretion of toxins. Some, like kidney stones and infections are highly treatable and are usually transient. Many others become chronic and ultimately lead to end-stage kidney failure, for which dialysis or renal transplant is required.

This module focuses on the most common renal diseases, that are most responsive to pharmaceutical intervention.

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Renal osteodystrophy (bone disease)

Bone health is regulated by several inter-connected pathways:

Calcium- required for bone strength, regulated by healthy kidney function
Phopshorus- key component of bone (as calcium phosphate), excess serum phosphate is removed in the kidneys
Calcitriol (active vitamin D)- regulates calcium absorption in the kidneys, and parathyroid gland function
Fibroblast growth factor 23 (FGF23)- produced in bones, regulates levels of phosphorus and vitamin D
Parathyroid hormone (PTH)- produced in the parathyroid glands, promotes calcium resorption from bones

Chronic kidney disease (CKD) severely disrupts normal mineral and bone regulatory processes, and is the leading cause of renal osteodystrophy. Failure of kidney function results in calcium and phosphorous retention, elevated PTH levels and vitamin D loss, all of which affect the processes of bone turnover and mineralisation. The condition is characterised by altered bone morphology and loss of structural integrity, with fragile bones that are easily fractured, and extraskeletal calcifications. The pattern of histological bone alterations caused by renal osteodystrophy is known as osteitis fibrosa, and are associated with secondary hyperparathyroidism-induced high bone turnover.

The development of renal osteodystrophy is inevitable in patients with CKD, but appropriate and timely interventions can help alleviate symptoms and reduce osteodystrophy-related comorbidities (arteriosclerosis and subsequent cardiovascular events). Treatment of renal osteodystrophy focuses on the strict control of phosphate, calcium, vitamin D, and PTH.

Management of renal osteodystrophy

Serum phosphate is regulated by initiating a phosphorous-restricted diet, with phosphate binders utilised to complement dietary restriction. Calcium acetate is the first choice, or sevelamer (a non-calcium-containing phosphate binder) if hypercalcemia and low PTH are present. Ferric citrate also has comparable phosphate control efficacy to sevelamer and to calcium acetate. Lanthanum is a poorly permeable trivalent cation that is highly effective in the treatment of hyperphosphatemia. Lanthanum should only be considered as a step-up intervention when other phosphate binders cannot be used.

Serum calcium is regulated by changing the concentration of calcium in the dialysate.

Vitamin D supplementation is used to reduce PTH-induced osteoblast activity. The primary toxicity associated with the potent vitamin D analogue calcitriol reflects its potent effect in increasing intestinal absorption of calcium and phosphate. Hypercalcemia, with or without hyperphosphatemia, often complicates calcitriol therapy and may limit its use at doses that effectively suppress PTH secretion. Calcitriol can cause hypercalcemia and hyperphosphatemia, and treatment should be stopped if serum phosphate rises above 5.5 mg/dL Other vitamin D analogues in clinical use include paricalcitol and falecalcitriol. Paricalcitol reduces serum PTH levels without causing hypercalcemia or altering serum phosphorus and is used to treat secondary hyperparathyroidism in patients with CKD.

Cinacalcet (a positive allosteric activator of the calcium-sensing receptor, CaSR) reduces PTH secretion and production, and can be used in a treatment regimen to achieve target PTH levels in dialysis patients.

Sodium bicarbonate is used to control acidosis.

Ultimately, if serum PTH cannot be controlled, surgical removal of part of the parathyroid gland (parathyroidectomy) may be considered, with subtotal removal recommended to preserve some PTH production.

Patients with end-stage renal disease (ESRD) can manifest diseases of low bone turnover, such as osteomalacia and adynamic bone disease, in which PTH is suppressed. The management strategy for these patients is different from that for hyperparathyroidism-induced high bone turnover osteodystrophy. Non-calcium-containing phosphate binders are preferred, to control phosphate levels without increasing calcium (which would further suppress PTH). Chelation with desferrioxamine can be started if aluminum-induced osteomalacia is suspected.

Overview of chronic kidney disease-mineral and bone disorder (CKD-MBD)

This is an in-depth overview of mineral and bone disorder associated with chronic kidney disease, that reviews the management of the condition in dialysis patients. It is maintained by UpToDate, and is regularly updated by experts. This resource is suitable for intermediate-advanced level learners and it provides links to additional pages covering management in nondialysis patients and those with end-stage kidney disease.